Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response

被引：144

作者：

Park, SG ^{[1
]}

Kim, HJ ^{[1
]}

Min, YH ^{[1
]}

Choi, EC ^{[1
]}

Shin, YK ^{[1
]}

Park, BJ ^{[1
]}

Lee, SW ^{[1
]}

Kim, S ^{[1
]}

机构：

[1] Seoul Natl Univ, Coll Pharm, Natl Creat Res Initiat Ctr ARS Network, Seoul 151742, South Korea

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2005年 / 102卷 / 18期

关键词：

aminoacyl-tRNA synthetase; cytokine; TNF-alpha; immune response; cell migration;

D O I：

10.1073/pnas.0500226102

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Although aminoacyl-tRNA synthetases (ARSs) are essential for protein synthesis, they also function as regulators and signaling molecules in diverse biological processes. Here, we screened 11 different human ARSs to identify the enzyme that is secreted as a signaling molecule. Among them, we found that lysyl-tRNA synthetase (KRS) was secreted from intact human cells, and its secretion was induced by TNF-alpha. The secreted KRS bound to macrophages and peripheral blood mononuclear cells to enhance the TNF-alpha production and their migration. The mitogen-activated protein kinases, extracellular signal-regulated kinase and p38 mitogen-activated protein kinase, and G alpha i were determined to be involved in the signal transduction triggered by KRS. All of these activities demonstrate that human KRS may work as a previously uncharacterized signaling molecule, inducing immune response through the activation of monocyte/macrophages.

引用

页码：6356 / 6361

页数：6

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